Wellbutrin vs. Lexapro: Differences, similarities, and which is better for you

In this article:

• Main differences
• Conditions treated
• Efficacy
• Coverage and cost
• Interactions
• Warnings
• FAQs

In this article

• Main differences
• Conditions treated
• Efficacy
• Coverage and cost
• Interactions
• Warnings
• FAQs

Wellbutrin and Lexapro are two prescription medications that are used in the treatment of major depressive disorder, or MDD. MDD is characterized by a low mood for at least two weeks in most situations. People with MDD may exhibit a loss of interest in activities they normally enjoy, low energy, or pain without any known cause. For some, counseling or physical activity may effectively control symptoms of depression, but for many, medication may be needed in addition to those lifestyle changes. 

Several types of medications treat depression. Wellbutrin is an aminoketone antidepressant that works by increasing available dopamine and norepinephrine, while Lexapro is a selective serotonin reuptake inhibitor (SSRI) that increases available serotonin. While both drugs work to treat depression, they do so by acting on different neurotransmitters which affect mood. Learn more about the differences below.

Main differences between Wellbutrin and Lexapro
	Wellbutrin	Lexapro
Drug class	Aminoketone antidepressant	Selective serotonin reuptake inhibitor
Brand/generic status	Brand and generic available	Brand and generic available
What is the generic name?	Bupropion	Escitalopram
What form(s) does the drug come in?	Immediate-release, sustained-release, and extended-release tablet	Oral tablet and oral solution
What is the standard dosage?	150 mg once per day	10 mg once per day
How long is the typical treatment?	Long-term (months to years)	Long-term (months to years)
Who typically uses the medication?	Adults (some off-label use in adolescents)	Adolescents and adults

What are the main differences between Wellbutrin and Lexapro?

Wellbutrin (bupropion) is a prescription medication indicated in the treatment of MDD and seasonal affective disorder. The active ingredient, bupropion, is also approved for use in smoking cessation in its sustained-release formulation. This was previously marketed under the brand name Zyban. Wellbutrin works as a dopamine and norepinephrine reuptake inhibitor at the neuronal level. This leaves higher levels of each neurotransmitter freely available, and dopamine and norepinephrine levels play an important role in mood and affect.

Wellbutrin is available in immediate-release tablets in 75 mg and 100 mg. The sustained-release tablet indicated for every 12-hour dosing is available in 100 mg, 150 mg, and 200 mg. The extended-release tablet indicated for once every 24-hour dosing is available in 150 mg and 300 mg.

Lexapro (escitalopram) is also a prescription medication indicated for the treatment of MDD. It belongs to the group of antidepressants known as SSRIs. Lexapro works by blocking the reuptake of serotonin at the neuronal membrane transport pump, effectively leaving more free serotonin in the neuron synapse. Other SSRIs you may be familiar with include Prozac, Zoloft, Celexa, or Paxil.

Lexapro is available as an oral tablet in strengths of 5 mg, 10 mg, and 20 mg and as an oral solution in a 5 mg/5 ml concentration.

Conditions treated by Wellbutrin and Lexapro

Wellbutrin and Lexapro are both indicated in the treatment of major depression. MDD is characterized by prolonged (2 weeks or more) feelings of low mood and decreased energy levels. It is possible that patients may not find joy in things they enjoyed previously. 

Lexapro is also indicated in the treatment of generalized anxiety disorder (GAD). GAD is characterized by prolonged and obsessive worrying about a variety of topics.

Bupropion, the active ingredient in Wellbutrin, carries a unique indication for smoking cessation. Although the mechanism is not entirely understood, patients taking bupropion are more likely to be able to achieve smoking cessation. A systematic review of numerous studies with an overall large sample size supports this statement, though patients may experience more adverse events than with other smoking cessation interventions.

Wellbutrin and Lexapro are both used off-label in a variety of psychological disorders that are closely related to depression. The following is not intended to be a complete listing of potential uses for Wellbutrin and Lexapro. Only your healthcare professional can diagnose your disorder and decide which treatment option is best for you.

Condition	Wellbutrin	Lexapro
Major depressive disorder	Yes	Yes
Seasonal affective disorder	Yes	No
Smoking cessation	Yes	No
Generalized anxiety disorder	No	Yes
Attention-deficit disorder	Off-label	No
Bipolar depression	Off-label	No
Augmentation of SSRI induced sexual dysfunction	Off-label	No
ADHD	Off-label	No
Neuropathic pain	Off-label	No
Cocaine dependence	Off-label	No
Amphetamine stimulant use disorder	Off-label	No
Irritability in Autism	No	Off-label
Binge eating disorder	No	Off-label
Bulimia nervosa	No	Off-label
Obsessive-compulsive Disorder	No	Off-label
Panic disorder	No	Off-label
Post-traumatic stress disorder	No	Off-label
Premenstrual dysphoric disorder	No	Off-label
Premature ejaculation	No	Off-label
Social anxiety disorder	No	Off-label

Is Wellbutrin or Lexapro more effective?

Researchers have sought to compare Wellbutrin and Lexapro as singular therapies for MDD, and together as dual therapy. One trial evaluated the efficacy of Wellbutrin as a single therapy compared to Lexapro single therapy. This study also sought to compare the prevalence of negative sexual side effects. The results found that Wellbutrin and Lexapro produced similar improvements in depressive symptoms. However, Wellbutrin was significantly less likely to cause sexual dysfunction.

Wellbutrin and Lexapro affect different neurotransmitters and are oftentimes used together. The results of one clinical trial found that the use of both drugs together leads to significantly higher response and symptom remission rates as compared to typical monotherapy with SSRIs. While further studies may be warranted, this study suggests some value in dual therapy with both medications.

Coverage and cost comparison of Wellbutrin vs. Lexapro

Wellbutrin is a prescription medication typically covered by commercial and Medicare drug plans. The out-of-pocket price for one month of Wellbutrin XL 150 mg can be more than $3,200, but with a coupon from SingleCare, you could get the generic for less than $10.

Lexapro is also a prescription medication typically covered by both commercial and Medicare drug plans. Similar to Wellbutrin, the out-of-pocket price for a 30-day supply of Lexapro 10 mg can be as much as $550. SingleCare offers a coupon for generic Lexapro, which lowers the price to $8.

	Wellbutrin	Lexapro
Typically covered by insurance?	Yes	Yes
Typically covered by Medicare?	Yes	Yes
Standard dosage	30, 150 mg XL tablets	30, 10 mg tablets
Typical Medicare copay	Less than $10	Less than $10
SingleCare cost	$10-$27	$8-$21

Common side effects of Wellbutrin vs. Lexapro

Wellbutrin and Lexapro affect the levels of different neurotransmitters. While their potential to cause certain side effects may be similar, there are some key differences. 

Lexapro, like other SSRIs, has the potential to cause decreased libido or sex drive. Wellbutrin had no reported incidence of decreased libido. Some researchers estimate that up to 80% of the side effects of SSRIs are related to sexual dysfunction. Compliance is an important factor in treating depression, so awareness of this side effect is important in managing a patient’s therapy.

Wellbutrin causes headaches in as many as a quarter of the patients who take it, while headaches were not reported with Lexapro. Both Wellbutrin and Lexapro may cause nausea, vomiting, sweating, and diarrhea.

The following list is not intended to be a complete list of adverse events. Please consult a pharmacist, healthcare provider, or another medical professional for a complete list of possible side effects.

	Wellbutrin		Lexapro
Side effect	Applicable?	Frequency	Applicable?	Frequency
Asthenia	Yes	2%	No	n/a
Nausea	Yes	13%	Yes	5%
Dry mouth	Yes	17%	Yes	5%
Sweating	Yes	6%	Yes	5%
Vomiting	Yes	4%	No	n/a
Diarrhea	Yes	5%	Yes	8%
Constipation	Yes	10%	Yes	3%
Dyspepsia	No	n/a	Yes	3%
Dizziness	Yes	7%	No	n/a
Somnolence	Yes	2%	Yes	6%
Agitation	Yes	3%	No	n/a
Headache	Yes	26%	No	n/a
Decreased appetite	Yes	5%	Yes	3%
Decreased libido	No	n/a	Yes	2%
Weight loss	Yes	14%	No	n/a
Weight gain	Yes	3%	No	n/a

Source: Wellbutrin (DailyMed) Lexapro (DailyMed)

Drug interactions of Wellbutrin vs. Lexapro

Wellbutrin is a major substrate of CYP2B6 and a strong inhibitor of CYP2D6. If co-administration of Wellbutrin and a CYP2D6 substrate is needed, the dose of the 2D6 substrate may need to be decreased. Some examples of CYP2D6 substrates include fluoxetine, sertraline, haloperidol, risperidone, and metoprolol.

Lexapro is a major substrate of CYP2C19 and CYP3A4 and a weak inhibitor of CYP2D6.

The use of Lexapro with tricyclic antidepressants, such as amitriptyline, may increase the risk of QT prolongation and serotonin syndrome. In general, this combination should be avoided. 

The following list is not intended to be a complete list of drug interactions. It is best to consult your provider or pharmacist for a complete list.

Drug	Drug Class	Wellbutrin	Lexapro
Acalabrutinib Dabrafenib Erdafitinib Gilteritinib Ibrutinib	Antineoplastics	Yes	Yes
Almotriptan Eletriptan Oxitriptan	5HT Agonist / Triptans (antimigraine agents)	No	Yes
Dexmethylphenidate Methylphenidate	Amphetamines	No	Yes
Alosetron Ondansetron Ramosetron	5HT3 Antagonists (anti-nausea agents)	No	Yes
Apixaban Edoxaban	Antiplatelets	No	Yes
Aripiprazole	Antipsychotic	Yes	Yes
Aspirin Ibuprofen Naproxen Diclofenac	Nonsteroidal anti-inflammatory drugs (NSAIDs)	No	Yes
Atomoxetine	Selective norepinephrine reuptake inhibitor (SNRI)	Yes	No
Bemiparin Enoxaparin Heparin	Anticoagulants	No	Yes
Bupropion	Dopamine/ norepinephrine reuptake inhibitor	No	Yes
Buspirone	Antianxiety	No	Yes
Carbamazepine	Anticonvulsant	Yes	Yes
Enzalutamide	Chemotherapy agent	No	Yes
Esomeprazole Omeprazole	Proton pump inhibitor	No	Yes
Fluconazole	Antifungal	No	Yes
Fluoxetine Duloxetine Paroxetine Sertraline	SSRIs	Yes	Yes
Hydroxychloroquine	Aminoquinolone/ Antimalarial	No	Yes
Linezolid	Antibiotic	No	Yes
Cyclobenzaprine Metaxalone	Muscle relaxers	No	Yes
Pimozide	Antipsychotic	No	Yes
Selegiline Phenelzine Rasagiline	Monoamine oxidase inhibitor (MAOI)	No	Yes
St. John’s Wort	Herbal supplement	No	Yes
Hydrochlorothiazide Chlorthalidone Metolazone	Thiazide diuretics	No	Yes
Tramadol	Opiate pain reliever	Yes	Yes
Amitriptyline Clomipramine Doxepin Nortriptyline	Tricyclic antidepressants	Yes	Yes
Venlafaxine	Selective norepinephrine reuptake inhibitor (SNRI)	No	Yes

Warnings of Wellbutrin and Lexapro

Patients with MDD may experience a worsening of depression or suicidal thoughts whether or not they are taking antidepressant medications. These conditions may worsen until remission is achieved. Wellbutrin and Lexapro therapy may increase suicidal ideation and thoughts among teens and young adults, especially in the early stages of treatment before any type of remission is achieved. These patients must be monitored closely if this treatment is deemed medically necessary. A therapy change may be necessary if symptoms suddenly arise or get worse.

Patients taking bupropion products for smoking cessation and who have no previous history of depression may experience mental changes when they initiate therapy. These can include mood changes, hallucinations, paranoia, delusions, aggression, and anxiety. If this occurs, speak with your healthcare provider immediately. 

In the case of both Wellbutrin and Lexapro, depression symptoms do not start to resolve immediately. Typically, changes in symptoms take a minimum of two weeks to observe, with most patients needing at least four to six weeks to see if the drug impacts their symptoms.

Wellbutrin can increase the risk of seizure. This increased risk is dose-dependent, and the maximum total daily dose should not exceed 300 mg. Wellbutrin may also be responsible for increased cardiovascular events. Patients on Wellbutrin may experience increased blood pressure, leading to hypertension, even if they had no previous cardiovascular diagnoses.

Serotonin syndrome, though rare, has been reported with all SSRIs, including Lexapro. This is a condition related to abnormally high levels of serotonin and can result in the patient feeling agitated, dizzy, and having an increased heart rate. This can be brought on by the use of two serotonergic drugs together. It is important to refer to the manufacturer’s information on drug interactions when prescribing these drugs.

Frequently asked questions about Wellbutrin vs. Lexapro

Are Wellbutrin and Lexapro the same?

While both Wellbutrin and Lexapro treat depression, they are not the same type of drug. Wellbutrin blocks the reuptake of dopamine and norepinephrine in the neuronal synapse, while Lexapro blocks serotonin reuptake. All of these neurotransmitters play a role in mood and affect.

Is Wellbutrin or Lexapro better?

In comparative studies, Wellbutrin and Lexapro provided similar improvement rates in depression measurement scales. Wellbutrin may have fewer side effects, specifically related to libido, and therefore, may be the better choice for some patients.

Does Lexapro or Wellbutrin make you gain weight?

Antidepressant use has generally been related to some weight change with long-term use, though it can be hard to correlate the reason. Many patients experiencing depression experience weight changes before treatment, and this can include both weight loss and weight gain. For some, depression can lead to a loss of appetite and unhealthy weight loss, and by treating depressive symptoms, their appetite may return to normal levels. There is evidence to show that Wellbutrin is less likely to cause weight gain than serotonergic antidepressants such as Lexapro. Weight management in depression involves many aspects of treatment, and you should discuss weight change concerns with your prescriber.

Can I use Wellbutrin or Lexapro while pregnant?

Wellbutrin is categorized as pregnancy category B by the Food and Drug Administration (FDA), meaning it is generally considered safe during pregnancy. Bupropion and its metabolites do cross the human placenta. Lexapro is pregnancy category C, meaning there have not been adequate human studies to determine efficacy. Animal studies have shown teratogenic effects on the fetus, including cardiovascular effects, and it has been determined that Lexapro crosses the human placenta. For these reasons, the use of Wellbutrin or Lexapro in pregnancy must be weighed against potential harm to the fetus. 

Can I use Wellbutrin or Lexapro with alcohol?

Alcohol can increase the toxic effects of both Wellbutrin and Lexapro. Drinking alcohol while taking these drugs can cause significant psychomotor impairment, and for this reason, patients are advised to avoid alcohol if taking Wellbutrin or Lexapro. Alcohol specifically lowers the seizure threshold in patients taking Wellbutrin, and patients with a history of seizures should avoid this combination.